An open question is whether the metabolic changes associated with pathological states and their response to therapy can be observed by NMR spectroscopy. In this grant, we propose to develop Chemical Shift Imaging (CSI) techniques which will allow this question to be answered. To maximize the metabolic information which can be obtained in a clinical setting, procedures for acquiring spatially localized 31P and 1H spectra with the highest possible sensitivity will be integrated with new processing and display algorithms. The integration of these components will permit the metabolic information inherent in the spectra to be correlated with other clinical data, allowing the identification of the most significant spectral parameters. The sensitivity of the data will be improved by designing and building new rf coils, by installing proton decoupling for 31P spectroscopy and by extending water suppression techniques to use with 1H chemical shift imaging (CSI). New data processing procedures and software packages will also be developed for examination planning, automatic first pass analysis of the CSI data, quantifying individual spectra and producing metabolic images. The information in coil sensitivity maps, relaxation times and peak areas of individual spectra will be combined to produce absolute metabolic concentrations, which will then be correlated with the anatomy as depicted in the associated proton images. To test the procedures and build up a database of metabolite concentrations in normal tissue, 31P CSI will be applied to study muscle and brain of volunteers. In the case of brain, a comparison will also be made with the metabolic information provided by localized 1H spectroscopy. In the final years of the grant, the techniques will be applied to study two tumor systems: squamous cell carcinoma metastases of the neck and brain metastases. This will provide an opportunity to study tumor heterogeneity, to compare localized 31P and 1H spectra and to test the feasibility of applying our procedures in a clinical setting. As the procedures being developed in this grant are validated, they will be made available to other investigators so that they can be applied routinely in a clinical setting.